Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Targeting of HIF- to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,1*David R. Mole,1*Ya-Min Tian,1Michael I. Wilson,1Janine Gielbert,2Simon J. Gaskell,2Alexander von Kriegsheim,3Holger F. Hebestreit,3Mridul Mukherji,4Christopher J. Schofield,4Patrick H. Maxwell,1
Christopher W. Pugh,1
Peter J. Ratcliffe1
Hypoxia-inducible factor (HIF) is a transcriptional
complex that plays a central role in the regulation of gene expressionby oxygen. In oxygenated and iron replete cells, HIF- subunitsare
rapidly destroyed by a mechanism that involves ubiquitylationby the
von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex.This process is suppressed by hypoxia and iron chelation, allowingtranscriptional activation. Here we show that the interactionbetween
human pVHL and a specific domain of the HIF-1 subunitis regulated
through hydroxylation of a proline residue (HIF-1P564) by an enzyme
we have termed HIF- prolyl-hydroxylase (HIF-PH).An absolute
requirement for dioxygen as a cosubstrate and ironas cofactor suggests
that HIF-PH functions directly as a cellularoxygen sensor.
1 The Henry Wellcome Building of Genomic
Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
2 Michael Barber Centre for Mass Spectrometry,
Department of Chemistry, University of Manchester Institute of Science
and Technology, Manchester M60 1QD, UK.
3 Glycobiology Institute, University of Oxford,
South Parks Road, Oxford OX1 3QU, UK.
4 The Oxford
Centre for Molecular Sciences and The Dyson Perrins Laboratory,
University of Oxford, South Parks Road, Oxford OX1 3QY, UK.
*
These authors contributed equally to the work.
The contribution of the three senior authors was
equivalent.
To whom correspondence should be addressed.
E-mail: peter.ratcliffe{at}imm.ox.ac.uk,
cwpugh{at}enterprise.molbiol.ox.ac.uk,
pmaxwell{at}hammer.imm.ox.ac.uk
The editors suggest the following Related Resources on Science sites:
In Science Magazine
RESEARCH ARTICLES
Mircea Ivan, Keiichi Kondo, Haifeng Yang, William Kim, Jennifer Valiando, Michael Ohh, Adrian Salic, John M. Asara, William S. Lane, and William G. Kaelin, Jr. (20 April 2001) Science292 (5516), 464.
[DOI: 10.1126/science.1059817] |Abstract »|Full Text »|PDF »|Supplemental Data »
PERSPECTIVES
Hao Zhu and H. Franklin Bunn (20 April 2001) Science292 (5516), 449.
[DOI: 10.1126/science.1060849] |Summary »|Full Text »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Reduction of Reactive Oxygen Species Ameliorates Metabolism-Secretion Coupling in Islets of Diabetic GK Rats by Suppressing Lactate Overproduction.
M. Sasaki, S. Fujimoto, Y. Sato, Y. Nishi, E. Mukai, G. Yamano, H. Sato, Y. Tahara, K. Ogura, K. Nagashima, et al. (2013)
Diabetes
62, 1996-2003
|Abstract »|Full Text »|PDF »
DCNL1 Functions as a Substrate Sensor and Activator of Cullin 2-RING Ligase.
P. Heir, R. I. Sufan, S. N. Greer, B. P. Poon, J. E. Lee, and M. Ohh (2013)
Mol. Cell. Biol.
33, 1621-1631
|Abstract »|Full Text »|PDF »
Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1.
S. Pisarcik, J. Maylor, W. Lu, X. Yun, C. Undem, J. T. Sylvester, G. L. Semenza, and L. A. Shimoda (2013)
Am J Physiol Lung Cell Mol Physiol
304, L549-L561
|Abstract »|Full Text »|PDF »
Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer.
Chaperone-mediated Autophagy Targets Hypoxia-inducible Factor-1{alpha} (HIF-1{alpha}) for Lysosomal Degradation.
M. E. Hubbi, H. Hu, Kshitiz, I. Ahmed, A. Levchenko, and G. L. Semenza (2013)
J. Biol. Chem.
288, 10703-10714
|Abstract »|Full Text »|PDF »
Prolyl Hydroxylase Domain Protein 2 (PHD2) Binds a Pro-Xaa-Leu-Glu Motif, Linking It to the Heat Shock Protein 90 Pathway.
D. Song, L.-S. Li, K. J. Heaton-Johnson, P. R. Arsenault, S. R. Master, and F. S. Lee (2013)
J. Biol. Chem.
288, 9662-9674
|Abstract »|Full Text »|PDF »
p62/SQSTM1 regulates cellular oxygen sensing by attenuating PHD3 activity through aggregate sequestration and enhanced degradation.
K. Rantanen, J.-P. Pursiheimo, H. Hogel, P. Miikkulainen, J. Sundstrom, and P. M. Jaakkola (2013)
J. Cell Sci.
126, 1144-1154
|Abstract »|Full Text »|PDF »
Identification of CDCP1 as a hypoxia-inducible factor 2{alpha} (HIF-2{alpha}) target gene that is associated with survival in clear cell renal cell carcinoma patients.
B. M. Emerling, C. H. Benes, G. Poulogiannis, E. L. Bell, K. Courtney, H. Liu, R. Choo-Wing, G. Bellinger, K. S. Tsukazawa, V. Brown, et al. (2013)
PNAS
110, 3483-3488
|Abstract »|Full Text »|PDF »
The Kaposi's Sarcoma-Associated Herpesvirus ORF34 Protein Binds to HIF-1{alpha} and Causes Its Degradation via the Proteasome Pathway.
H. F. Bunn (2013)
J. Biol. Chem.
288, 5062-5071
|Full Text »|PDF »
A Nontranscriptional Role for HIF-1{alpha} as a Direct Inhibitor of DNA Replication.
M. E. Hubbi, Kshitiz, D. M. Gilkes, S. Rey, C. C. Wong, W. Luo, D.-H. Kim, C. V. Dang, A. Levchenko, and G. L. Semenza (2013)
Science Signaling
6, ra10
|Abstract »|Full Text »|PDF »
Impact of the Hypoxia-Inducible Factor-1 {alpha} (HIF1A) Pro582Ser Polymorphism on Diabetes Nephropathy.
H. F. Gu, X. Zheng, N. Abu Seman, T. Gu, I. R. Botusan, V. G. Sunkari, E. F. Lokman, K. Brismar, and S.-B. Catrina (2013)
Diabetes Care
36, 415-421
|Abstract »|Full Text »|PDF »
Pharmacologic stabilization of HIF-1{alpha} increases hematopoietic stem cell quiescence in vivo and accelerates blood recovery after severe irradiation.
C. E. Forristal, I. G. Winkler, B. Nowlan, V. Barbier, G. Walkinshaw, and J.-P. Levesque (2013)
Blood
121, 759-769
|Abstract »|Full Text »|PDF »
Hypoxia and Adipose Tissue Function and Dysfunction in Obesity.
The Effect of Long Term Calorie Restriction on in Vivo Hepatic Proteostatis: A Novel Combination of Dynamic and Quantitative Proteomics.
J. C. Price, C. F. Khambatta, K. W. Li, M. D. Bruss, M. Shankaran, M. Dalidd, N. A. Floreani, L. S. Roberts, S. M. Turner, W. E. Holmes, et al. (2012)
Mol. Cell. Proteomics
11, 1801-1814
|Abstract »|Full Text »|PDF »
Identification of a Signaling Axis HIF-1{alpha}/MicroRNA-210/ISCU Independent of SDH Mutation That Defines a Subgroup of Head and Neck Paragangliomas.
A. Merlo, S. B. de Quiros, P. Secades, I. Zambrano, M. Balbin, A. Astudillo, B. Scola, M. Aristegui, C. Suarez, and M.-D. Chiara (2012)
J. Clin. Endocrinol. Metab.
97, E2194-E2200
|Abstract »|Full Text »|PDF »
The TNF-{alpha}/ROS/HIF-1-induced Upregulation of FoxMI Expression Promotes HCC Proliferation and Resistance to Apoptosis.
L. Xia, P. Mo, W. Huang, L. Zhang, Y. Wang, H. Zhu, D. Tian, J. Liu, Z. Chen, Y. Zhang, et al. (2012)
Carcinogenesis
33, 2250-2259
|Abstract »|Full Text »|PDF »
Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics.
A. V. Hoffbrand, A. Taher, and M. D. Cappellini (2012)
Blood
120, 3657-3669
|Abstract »|Full Text »|PDF »
Transcriptional responses to hypoxia are enhanced by recurrent hypoxia (hypoxic preconditioning) in the epaulette shark.
K. T. Rytkonen, G. M. C. Renshaw, P. P. Vainio, K. J. Ashton, G. Williams-Pritchard, E. H. Leder, and M. Nikinmaa (2012)
Physiol Genomics
44, 1090-1097
|Abstract »|Full Text »|PDF »
Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis.
A. Laitala, E. Aro, G. Walkinshaw, J. M. Maki, M. Rossi, M. Heikkila, E.-R. Savolainen, M. Arend, K. I. Kivirikko, P. Koivunen, et al. (2012)
Blood
120, 3336-3344
|Abstract »|Full Text »|PDF »
Sorafenib Inhibits Hypoxia-Inducible Factor-1{alpha} Synthesis: Implications for Antiangiogenic Activity in Hepatocellular Carcinoma.
L.-p. Liu, R. L. K. Ho, G. G. Chen, and P. B. S. Lai (2012)
Clin. Cancer Res.
18, 5662-5671
|Abstract »|Full Text »|PDF »
Activation of Peroxisome Proliferator-activated Receptor {alpha} (PPAR{alpha}) Suppresses Hypoxia-inducible Factor-1{alpha} (HIF-1{alpha}) Signaling in Cancer Cells.
J. Zhou, S. Zhang, J. Xue, J. Avery, J. Wu, S. E. Lind, and W.-Q. Ding (2012)
J. Biol. Chem.
287, 35161-35169
|Abstract »|Full Text »|PDF »
Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells.
L. Schito, S. Rey, M. Tafani, H. Zhang, C. C.-L. Wong, A. Russo, M. A. Russo, and G. L. Semenza (2012)
PNAS
109, E2707-E2716
|Abstract »|Full Text »|PDF »
Glucotoxicity Induces Glucose-6-Phosphatase Catalytic Unit Expression by Acting on the Interaction of HIF-1{alpha} With CREB-Binding Protein.
A. Gautier-Stein, M. Soty, J. Chilloux, C. Zitoun, F. Rajas, and G. Mithieux (2012)
Diabetes
61, 2451-2460
|Abstract »|Full Text »|PDF »
Impacts of Hypoxia-Inducible Factor-1 Knockout in the Retinal Pigment Epithelium on Choroidal Neovascularization.
M. Lin, Y. Hu, Y. Chen, K. K. Zhou, J. Jin, M. Zhu, Y.-Z. Le, J. Ge, and J.-x. Ma (2012)
Invest. Ophthalmol. Vis. Sci.
53, 6197-6206
|Abstract »|Full Text »|PDF »
A Zebrafish Model to Study and Therapeutically Manipulate Hypoxia Signaling in Tumorigenesis.
K. Santhakumar, E. C. Judson, P. M. Elks, S. McKee, S. Elworthy, E. van Rooijen, S. S. Walmsley, S. A. Renshaw, S. S. Cross, and F. J. M. van Eeden (2012)
Cancer Res.
72, 4017-4027
|Abstract »|Full Text »|PDF »
The balance of beneficial and deleterious effects of hypoxia-inducible factor activation by prolyl hydroxylase inhibitor in rat remnant kidney depends on the timing of administration.
X. Yu, Y. Fang, H. Liu, J. Zhu, J. Zou, X. Xu, S. Jiang, and X. Ding (2012)
Nephrol. Dial. Transplant.
27, 3110-3119
|Abstract »|Full Text »|PDF »
Copper Is Required for Cobalt-Induced Transcriptional Activity of Hypoxia-Inducible Factor-1.
L. Qiu, X. Ding, Z. Zhang, and Y. J. Kang (2012)
J. Pharmacol. Exp. Ther.
342, 561-567
|Abstract »|Full Text »|PDF »
MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism.
H. Peng, R. B. Hamanaka, J. Katsnelson, L.-L. Hao, W. Yang, N. S. Chandel, and R. M. Lavker (2012)
FASEB J
26, 3140-3147
|Abstract »|Full Text »|PDF »
Statin inhibits hypoxia-induced endothelin-1 via accelerated degradation of HIF-1{alpha} in vascular smooth muscle cells.
T. Hisada, M. Ayaori, N. Ohrui, H. Nakashima, K. Nakaya, H. Uto-Kondo, E. Yakushiji, S. Takiguchi, Y. Terao, Y. Miyamoto, et al. (2012)
Cardiovasc Res
95, 251-259
|Abstract »|Full Text »|PDF »
Adaptive and Maladaptive Cardiorespiratory Responses to Continuous and Intermittent Hypoxia Mediated by Hypoxia-Inducible Factors 1 and 2.
The HIF-1{alpha} Hypoxia Response in Tumor-Infiltrating T Lymphocytes Induces Functional CD137 (4-1BB) for Immunotherapy.
A. Palazon, I. Martinez-Forero, A. Teijeira, A. Morales-Kastresana, C. Alfaro, M. F. Sanmamed, J. L. Perez-Gracia, I. Penuelas, S. Hervas-Stubbs, A. Rouzaut, et al. (2012)
Cancer Discovery
2, 608-623
|Abstract »|Full Text »|PDF »
Loss of Fibroblast HIF-1{alpha} Accelerates Tumorigenesis.
J.-w. Kim, C. Evans, A. Weidemann, N. Takeda, Y. S. Lee, C. Stockmann, C. Branco-Price, F. Brandberg, G. Leone, M. C. Ostrowski, et al. (2012)
Cancer Res.
72, 3187-3195
|Abstract »|Full Text »|PDF »
State of the Science: An Update on Renal Cell Carcinoma.
E. Jonasch, P. A. Futreal, I. J. Davis, S. T. Bailey, W. Y. Kim, J. Brugarolas, A. J. Giaccia, G. Kurban, A. Pause, J. Frydman, et al. (2012)
Mol. Cancer Res.
10, 859-880
|Abstract »|Full Text »|PDF »
Inhibition of {alpha}-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors.
M. Xiao, H. Yang, W. Xu, S. Ma, H. Lin, H. Zhu, L. Liu, Y. Liu, C. Yang, Y. Xu, et al. (2012)
Genes & Dev.
26, 1326-1338
|Abstract »|Full Text »|PDF »
Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease.
G. O. Ouma, R. A. Jonas, M. H. U. Usman, and E. R. Mohler III (2012)
Vascular Medicine
17, 174-192
|Abstract »|Full Text »|PDF »
Agents That Stabilize Mutated von Hippel-Lindau (VHL) Protein: Results of a High-Throughput Screen to Identify Compounds That Modulate VHL Proteostasis.
Z. Ding, P. German, S. Bai, Z. Feng, M. Gao, W. Si, M. M. Sobieski, C. C. Stephan, G. B. Mills, and E. Jonasch (2012)
J Biomol Screen
17, 572-580
|Abstract »|Full Text »|PDF »
Hypoxia-Inducible Factor-2{alpha} Activation Promotes Colorectal Cancer Progression by Dysregulating Iron Homeostasis.
X. Xue, M. Taylor, E. Anderson, C. Hao, A. Qu, J. K. Greenson, E. M. Zimmermann, F. J. Gonzalez, and Y. M. Shah (2012)
Cancer Res.
72, 2285-2293
|Abstract »|Full Text »|PDF »
JMJD5, a Jumonji C (JmjC) Domain-containing Protein, Negatively Regulates Osteoclastogenesis by Facilitating NFATc1 Protein Degradation.
M.-Y. Youn, A. Yokoyama, S. Fujiyama-Nakamura, F. Ohtake, K.-i. Minehata, H. Yasuda, T. Suzuki, S. Kato, and Y. Imai (2012)
J. Biol. Chem.
287, 12994-13004
|Abstract »|Full Text »|PDF »
Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest.
D. Z. Levett, E. J. Radford, D. A. Menassa, E. F. Graber, A. J. Morash, H. Hoppeler, K. Clarke, D. S. Martin, A. C. Ferguson-Smith, H. E. Montgomery, et al. (2012)
FASEB J
26, 1431-1441
|Abstract »|Full Text »|PDF »
Unfavourable consequences of chronic cardiac HIF-1{alpha} stabilization.
M. Holscher, K. Schafer, S. Krull, K. Farhat, A. Hesse, M. Silter, Y. Lin, B. J. Pichler, P. Thistlethwaite, A. El-Armouche, et al. (2012)
Cardiovasc Res
94, 77-86
|Abstract »|Full Text »|PDF »
Interaction with ErbB4 Promotes Hypoxia-inducible Factor-1{alpha} Signaling.
I. Paatero, A. Jokilammi, P. T. Heikkinen, K. Iljin, O.-P. Kallioniemi, F. E. Jones, P. M. Jaakkola, and K. Elenius (2012)
J. Biol. Chem.
287, 9659-9671
|Abstract »|Full Text »|PDF »
Prolyl Hydroxylase-dependent Modulation of Eukaryotic Elongation Factor 2 Activity and Protein Translation under Acute Hypoxia.
A. Romero-Ruiz, L. Bautista, V. Navarro, A. Heras-Garvin, R. March-Diaz, A. Castellano, R. Gomez-Diaz, M. J. Castro, E. Berra, J. Lopez-Barneo, et al. (2012)
J. Biol. Chem.
287, 9651-9658
|Abstract »|Full Text »|PDF »
Molecular Pathways: Hypoxia Response in Immune Cells Fighting or Promoting Cancer.
A. Palazon, J. Aragones, A. Morales-Kastresana, M. O. de Landazuri, and I. Melero (2012)
Clin. Cancer Res.
18, 1207-1213
|Abstract »|Full Text »|PDF »
Four-and-a-Half LIM Domain Proteins Inhibit Transactivation by Hypoxia-inducible Factor 1.
M. E. Hubbi, D. M. Gilkes, J. H. Baek, and G. L. Semenza (2012)
J. Biol. Chem.
287, 6139-6149
|Abstract »|Full Text »|PDF »
Myc Posttranscriptionally Induces HIF1 Protein and Target Gene Expression in Normal and Cancer Cells.
M. R. Doe, J. M. Ascano, M. Kaur, and M. D. Cole (2012)
Cancer Res.
72, 949-957
|Abstract »|Full Text »|PDF »
GSK-3{beta} regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1{alpha}.
HECT and RING finger families of E3 ubiquitin ligases at a glance.
M. B. Metzger, V. A. Hristova, and A. M. Weissman (2012)
J. Cell Sci.
125, 531-537
|Full Text »|PDF »
RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells.
B. Shan, J. Gerez, M. Haedo, M. Fuertes, M. Theodoropoulou, M. Buchfelder, M. Losa, G. K. Stalla, E. Arzt, and U. Renner (2012)
Endocr. Relat. Cancer
19, 13-27
|Abstract »|Full Text »|PDF »
Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1{alpha} and inhibits stromal cell-derived factor-1 in human endometrial stromal cells.
T. Tsuzuki, H. Okada, H. Cho, S. Tsuji, A. Nishigaki, K. Yasuda, and H. Kanzaki (2012)
Hum. Reprod.
27, 523-530
|Abstract »|Full Text »|PDF »
Digoxin inhibits development of hypoxic pulmonary hypertension in mice.
E. M. Abud, J. Maylor, C. Undem, A. Punjabi, A. L. Zaiman, A. C. Myers, J. T. Sylvester, G. L. Semenza, and L. A. Shimoda (2012)
PNAS
109, 1239-1244
|Abstract »|Full Text »|PDF »
Functional Interaction between Responses to Lactic Acidosis and Hypoxia Regulates Genomic Transcriptional Outputs.
X. Tang, J. E. Lucas, J. L.-Y. Chen, G. LaMonte, J. Wu, M. C. Wang, C. Koumenis, and J.-T. Chi (2012)
Cancer Res.
72, 491-502
|Abstract »|Full Text »|PDF »
M. Altun, B. Zhao, K. Velasco, H. Liu, G. Hassink, J. Paschke, T. Pereira, and K. Lindsten (2012)
J. Biol. Chem.
287, 1962-1969
|Abstract »|Full Text »|PDF »
Hypoxic Pulmonary Vasoconstriction.
J. T. Sylvester, L. A. Shimoda, P. I. Aaronson, and J. P. T. Ward (2012)
Physiol Rev
92, 367-520
|Abstract »|Full Text »|PDF »
Copper stimulates growth of human umbilical vein endothelial cells in a vascular endothelial growth factor-independent pathway.
Regulation of Cellular Levels of Sprouty2 Protein by Prolyl Hydroxylase Domain and von Hippel-Lindau Proteins.
K. Anderson, K. A. Nordquist, X. Gao, K. C. Hicks, B. Zhai, S. P. Gygi, and T. B. Patel (2011)
J. Biol. Chem.
286, 42027-42036
|Abstract »|Full Text »|PDF »
Iron deficiency in pulmonary arterial hypertension: a potential therapeutic target.
C. J. Rhodes, J. Wharton, L. Howard, J. S. R. Gibbs, A. Vonk-Noordegraaf, and M. R. Wilkins (2011)
Eur. Respir. J.
38, 1453-1460
|Abstract »|Full Text »|PDF »
The Novel Bcl-2 Inhibitor ABT-737 Is More Effective in Hypoxia and Is Able to Reverse Hypoxia-Induced Drug Resistance in Neuroblastoma Cells.
T. Klymenko, M. Brandenburg, C. Morrow, C. Dive, and G. Makin (2011)
Mol. Cancer Ther.
10, 2373-2383
|Abstract »|Full Text »|PDF »
Dihydroceramide-based Response to Hypoxia.
C. M. Devlin, T. Lahm, W. C. Hubbard, M. Van Demark, K. C. Wang, X. Wu, A. Bielawska, L. M. Obeid, M. Ivan, and I. Petrache (2011)
J. Biol. Chem.
286, 38069-38078
|Abstract »|Full Text »|PDF »
Lung Cell Hypoxia: Role of Mitochondrial Reactive Oxygen Species Signaling in Triggering Responses.
Tanshinone IIA-Induced Attenuation of Lung Injury in Endotoxemic Mice Is Associated with Reduction of Hypoxia-Inducible Factor 1{alpha} Expression.
M. Xu, F. Cao, L. Liu, B. Zhang, Y. Wang, H. Dong, Y. Cui, M. Dong, D. Xu, Y. Liu, et al. (2011) 45, 1028-1035
|Abstract »|Full Text »|PDF »
Generation of a Mouse Model of Von Hippel-Lindau Kidney Disease Leading to Renal Cancers by Expression of a Constitutively Active Mutant of HIF1{alpha}.
L. Fu, G. Wang, M. M. Shevchuk, D. M. Nanus, and L. J. Gudas (2011)
Cancer Res.
71, 6848-6856
|Abstract »|Full Text »|PDF »
Prolyl 4-hydroxylase genes are subjected to alternative splicing in roots of maize seedlings under waterlogging.
X. Zou, Y. Jiang, Y. Zheng, M. Zhang, and Z. Zhang (2011)
Ann. Bot.
108, 1323-1335
|Abstract »|Full Text »|PDF »
Interaction of HIF and USF Signaling Pathways in Human Genes Flanked by Hypoxia-Response Elements and E-box Palindromes.
J. Hu, D. P. Stiehl, C. Setzer, D. Wichmann, D. A. Shinde, H. Rehrauer, P. Hradecky, M. Gassmann, and T. A. Gorr (2011)
Mol. Cancer Res.
9, 1520-1536
|Abstract »|Full Text »|PDF »
Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury.
G. Schley, B. Klanke, J. Schodel, F. Forstreuter, D. Shukla, A. Kurtz, K. Amann, M. S. Wiesener, S. Rosen, K.-U. Eckardt, et al. (2011)
J. Am. Soc. Nephrol.
22, 2004-2015
|Abstract »|Full Text »|PDF »
A-kinase anchoring proteins: scaffolding proteins in the heart.
D. Diviani, K. L. Dodge-Kafka, J. Li, and M. S. Kapiloff (2011)
Am J Physiol Heart Circ Physiol
301, H1742-H1753
|Abstract »|Full Text »|PDF »
Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF.
E. Feige, S. Yokoyama, C. Levy, M. Khaled, V. Igras, R. J. Lin, S. Lee, H. R. Widlund, S. R. Granter, A. L. Kung, et al. (2011)
PNAS
108, E924-E933
|Abstract »|Full Text »|PDF »
Cell-Autonomous and Non-Cell-Autonomous Neuroprotective Functions of ROR{alpha} in Neurons and Astrocytes during Hypoxia.
S. Jolly, N. Journiac, F. Naudet, V. Gautheron, J. Mariani, and B. Vernet-der Garabedian (2011)
J. Neurosci.
31, 14314-14323
|Abstract »|Full Text »|PDF »
Silencing of Hypoxia-Inducible Factor-1{alpha} Gene Attenuated Angiotensin II-Induced Renal Injury in Sprague-Dawley Rats.
Q. Zhu, Z. Wang, M. Xia, P.-L. Li, B. W. Van Tassell, A. Abbate, R. Dhaduk, and N. Li (2011)
Hypertension
58, 657-664
|Abstract »|Full Text »|PDF »
Hypoxia-Inducible Factor 1 Is Activated by Dysregulated Cyclin E during Mammary Epithelial Morphogenesis.
T. Sengupta, G. Abraham, Y. Xu, B. E. Clurman, and A. C. Minella (2011)
Mol. Cell. Biol.
31, 3885-3895
|Abstract »|Full Text »|PDF »
Hypoxia-inducible factor-1 drives annexin A2 system-mediated perivascular fibrin clearance in oxygen-induced retinopathy in mice.
B. Huang, A. B. Deora, K.-L. He, K. Chen, G. Sui, A. T. Jacovina, D. Almeida, P. Hong, P. Burgman, and K. A. Hajjar (2011)
Blood
118, 2918-2929
|Abstract »|Full Text »|PDF »
Role of von Hippel-Lindau protein in fibroblast proliferation and fibrosis.
Q. Zhou, A. Pardo, M. Konigshoff, O. Eickelberg, G. R. S. Budinger, K. Thavarajah, C. J. Gottardi, J. Jones, J. Varga, M. Selman, et al. (2011)
FASEB J
25, 3032-3044
|Abstract »|Full Text »|PDF »
Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche.
M. Rehn, A. Olsson, K. Reckzeh, E. Diffner, P. Carmeliet, G. Landberg, and J. Cammenga (2011)
Blood
118, 1534-1543
|Abstract »|Full Text »|PDF »
MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6.
K. Saito, E. Kondo, and M. Matsushita (2011)
Nucleic Acids Res.
39, 6086-6099
|Abstract »|Full Text »|PDF »
Mechanism of CRL4Cdt2, a PCNA-dependent E3 ubiquitin ligase.
Normoxic Activation of Hypoxia-Inducible Factors in Photoreceptors Provides Transient Protection against Light-Induced Retinal Degeneration.
C. Lange, S. R. Heynen, N. Tanimoto, M. Thiersch, Y.-Z. Le, I. Meneau, M. W. Seeliger, M. Samardzija, C. Caprara, and C. Grimm (2011)
Invest. Ophthalmol. Vis. Sci.
52, 5872-5880
|Abstract »|Full Text »|PDF »
Activation of hypoxia-inducible factor-1{alpha} (Hif-1{alpha}) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model.
P. M. Elks, F. J. van Eeden, G. Dixon, X. Wang, C. C. Reyes-Aldasoro, P. W. Ingham, M. K. B. Whyte, S. R. Walmsley, and S. A. Renshaw (2011)
Blood
118, 712-722
|Abstract »|Full Text »|PDF »
A Hypoxia-Induced Positive Feedback Loop Promotes Hypoxia-Inducible Factor 1{alpha} Stability through miR-210 Suppression of Glycerol-3-Phosphate Dehydrogenase 1-Like.
T. J. Kelly, A. L. Souza, C. B. Clish, and P. Puigserver (2011)
Mol. Cell. Biol.
31, 2696-2706
|Abstract »|Full Text »|PDF »
Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2{alpha} gain-of-function mutation.
F. Formenti, P. A. Beer, Q. P. P. Croft, K. L. Dorrington, D. P. Gale, T. R. J. Lappin, G. S. Lucas, E. R. Maher, P. H. Maxwell, M. F. McMullin, et al. (2011)
FASEB J
25, 2001-2011
|Abstract »|Full Text »|PDF »
Anti-inflammatory actions of adrenomedullin through fine tuning of HIF stabilization.
C. F. MacManus, E. L. Campbell, S. Keely, A. Burgess, D. J. Kominsky, and S. P. Colgan (2011)
FASEB J
25, 1856-1864
|Abstract »|Full Text »|PDF »
Hypoxia Stimulates Low-Density Lipoprotein Receptor-Related Protein-1 Expression Through Hypoxia-Inducible Factor-1{alpha} in Human Vascular Smooth Muscle Cells.
J. Castellano, R. Aledo, J. Sendra, P. Costales, O. Juan-Babot, L. Badimon, and V. Llorente-Cortes (2011)
Arterioscler Thromb Vasc Biol
31, 1411-1420
|Abstract »|Full Text »|PDF »
to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Christopher W. Pugh,
subunits are
rapidly destroyed by a mechanism that involves ubiquitylation by the
von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. Here we show that the interaction between
human pVHL and a specific domain of the HIF-1
